Immunity to parasitic diseases Dr Eman Albataineh Associate

Immunity to parasitic diseases Dr. Eman Albataineh, Associate Prof. Immunology College of Medicine, Mutah university Immunology,

Effector mechanisms by Immune cells MACROPHAGES • Provide strong defense against small parasites • Secrete factors that kill parasites without ingestion • Secrete cytokines that activate other immune cells • Synthesize nitric oxide that act as parasite toxin • Activation of macrophages is a general feature of early stage of infection

NEUTROPHILS • Can kill large and small parasites • Phagocytic activation • Have granules that contain cytotoxic proteins • Have Fc and complement receptors >> ADCC PLATELETS • Cytotoxic activities against larval stages • Activation are enhanced by cytokines

EOSINOPHILS • Characterize parasitic infection • Thought to be specific against tissue parasites • Limit migration of parasites through the host • Less phagocytic than neutrophils • Act in accordance with mast cells

Role of T cells • The type of T cells involved is determined by the type and the stage of the infection • Cytokines enhance protective immunity against intracellular parasites • T helper 2 cells are essential for the elimination of intestinal worms

Role of Antibodies • Parasites induce production of specific and non specific Abs • Antibodies have several functions on parasites -Act directly on protozoa -Block attachment to host cells -Important for Phagocytosis

• parasites currently account for greater morbidity and mortality than any other class of infectious organisms, particularly in developing countries. • Most parasites go through complex life cycles, part of which occurs in humans (or other vertebrates) and part of which occurs in intermediate hosts, such as flies, ticks, and snails. • For instance, malaria and trypanosomiasis are transmitted by insect bites, and schistosomiasis is transmitted by exposure to water in which infected snails reside. • Most parasitic infections are chronic because of weak innate immunity and the ability of parasites to evade or resist elimination by adaptive immune responses.

Innate immunity • The principal innate immune response to protozoa is phagocytosis, but many of these parasites are resistant to phagocytic killing and may even replicate within macrophages. • Some protozoa express surface molecules that are recognized by TLRs and activate phagocytes. Plasmodium species (the protozoa that are responsible for malaria), Toxoplasma gondii (the agent that causes toxoplasmosis), and Cryptosporidium species (the major parasite that causes diarrhea in HIV-infected patients) all express glycosyl phosphatidylinositol lipids that can activate TLR 2 and TLR 4. • Phagocytes may also attack helminthic parasites and secrete microbicidal substances to kill organisms that are too large to be phagocytosed. • However, many helminths have thick teguments and very large to be phagocytosed • Many developed resistance to complement mediated lysis.

Adaptive immunity • Resistance to the infection is associated with activation of Leishmania specific CD 4+ TH 1 cells, which produce IFN-γ and thereby activate macrophages to destroy intracellular parasites. • Protozoa that replicate inside various host cells and lyse these cells stimulate specific antibody and CTL responses, similar to cytopathic viruses. An example of such an organism is the malaria parasite The • cytokine IFN-γ has been shown to be protective in many protozoal infections, including malaria, toxoplasmosis, and cryptosporidiosis. • Defense against many helminthic infections is mediated by the activation of TH 2 cells, which results in production of Ig. E antibodies and activation of eosinophils, which secrete IL-4 and IL-5. • Adaptive immune responses to parasites can also contribute to tissue injury. Some parasites and their products induce granulomatous responses with concomitant fibrosis. Schistosoma mansoni eggs in liver cirrhosis • In lymphatic filariasis, lodging of the parasites in lymphatic vessels leads to chronic cell mediated immune reactions and ultimately to fibrosis • Immune complex disease is a complication of schistosomiasis and malaria.

Immune evasion • Parasites change their surface antigens during their life cycle in vertebrate hosts. Two forms of antigenic variation are well defined. The first is a stage-specific change in antigen expression, such that the mature tissue stages of parasites produce antigens different from those of the infective stages as malaria • The second and more remarkable example of antigenic variation in parasites is the continuous variation of major surface antigens seen in African trypanosomes such as Trypanosoma brucei and Trypanosoma rhodesiense. Continuous antigenic variation in trypanosomes is mainly due to changes in expression of the genes

Immune evasion • schistosome larvae, which travel to the lungs of infected animals and during this migration develop a tegument that is resistant to damage by complement and by CTLs • Protozoan parasites may conceal themselves from the immune system either by living inside host cells or by developing cysts that are resistant to immune effectors as helminthic parasites reside in intestinal lumens • Shedding of antigens renders the parasites resistant to subsequent antibody-mediated attack. Entamoeba histolytica is a protozoan parasite that sheds antigens • Parasites inhibit host immune responses. T cell anergy to parasite antigens has been observed in severe schistosomiasis and in filarial infections. • Some parasites, such as Leishmania, stimulate the development of regulatory T cells, . • More non-specific and generalized immunosuppression is observed in malaria and African trypanosomiasis. This immune deficiency has been attributed to the production of immunosuppressive cytokines